Antiallergic agent

ABSTRACT

This invention is to provide an agent for therapy and prevention of allergic diseases which has no adverse action, shows a high safety even by administration for a long period and is able to be utilized to food and/or beverage, cosmetics, etc. which are used daily. To be specific, it provides antiallergic agent and anti-inflammatory agent characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient; a method for the addition of an antiallergic agent for oral administration or an anti-inflammatory agent for oral administration which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient to food and/or beverage for prevention, suppression and mitigation of allergic symptoms or inflammatory symptoms.

FIELD OF THE INVENTION

[0001] The present invention relates to a pharmaceutical agent as wellas food and/or beverage and cosmetics containing at least one polyphenolcompound selected from strictinin and methylated derivatives thereof asan effective ingredient and, more particularly, it relates to a foodhaving an action of suppressing the immediate-type and delayed-typeallergy, to a pharmaceutical agent with an object of improving theallergy and to a cosmetic agent containing the same.

BACKGROUND OF THE INVENTION

[0002] In recent years, an increase in allergic diseases has been notedand it is reported that, in about one-third of the newborn babies, onsetof atopic dermatitis or asthma is observed. A drastic increase in onsetof pollinosis has been becoming a big social problem as well.

[0003] It has been believed that changes of environment surrounding ussuch as westernization of meals, air pollution, food additives andexcessive stress are the causes of an increase in such allergicsymptoms.

[0004] In view of the immunological competent cell and immunoglobulinwhich are participated therein, allergic reaction is classified intofrom type I to type IV. Diseases represented by allergic rhinitis andbronchial asthma belong to the allergic reaction of type I where IgEantibody is produced in large quantities when exposed to allergen andchemical mediators such as histamine, leukotrienes and prostaglandin areproduced and released from mast cells and basophils via the said IgEantibody whereby dilation of blood vessel, promotion of blood vesselpermeability, shrinking of bronchial smooth muscles, stimulation ofnerve terminals, etc. are induced. Therefore, for the therapy ofallergic diseases of type I, antihistaminic agents and antiallergicagents having an action of suppressing the liberation of chemicalmediators from mast cells have been used.

[0005] However, antihistaminic agents and basic antiallergic agents haveadverse actions such as drowsiness, thirst, gastrointestinal troubles,etc. and their continuous administration for a long period causes aproblem.

[0006] Allergic reaction of type IV is a reaction of a delayed type inwhich T cells are participated where T cells receiving an antigeninformation via antigen-presenting cells such as Langerhans cells andmacrophage produce and release various cytokines whereby an inflammationreaction of a delayed type takes place due to accumulation ofeosinophils and macrophages.

[0007] Allergic contact dermatitis is a typical disease which occurs dueto an allergic reaction of type IV. Steroid agents are used for thetherapy of allergic diseases of type IV and such steroid agents suppressthe production of cytokine in T cells and show a dramatic effect for thetherapy of eczema. On the other hand however, there is a possibilitythat they cause severe adverse actions such as a decrease inadrenocortical function, flushing of the skin, atrophy and dilation ofcapillaries by their administration for a long period.

[0008] In the meanwhile, tea is a typical luxurious beverage and hasbeen drunk by many people during more than 2000 years. It has been alsoknown that tea has various physiological functions and, for example, itsantioxidative action, antitumor action, suppressive action tocarcinogenesis, antibacterial action, antiviral action and anticariousaction have been reported.

[0009] With regard to an allergic action, there have been exemplifiedthe therapeutic agent to the allergic reaction of type I as anantiallergic agent mainly comprising an extract from oolong tea using anaction of suppressing the histamine liberation from mast cells as anindicator in Japanese Patent Laid-Open No. 258726/1991; the effectivecases of natural caffeine for the promoting reaction of blood vesselpermeability in allergic symptom of type I in Japanese Patent Laid-OpenNo. 17865/1995; and therapeutic agents such as antiallergic agent,anti-inflammatory agent, anti-atopic dermatitis agent and anti-psoriasiswhere an extract of oolong tea is an effective ingredient in JapanesePatent Laid-Open Nos. 77231/1998 and 175874/1998.

[0010] It has been further reported that green tea catechins such asepigallocatechin gallate and epicatechin gallate suppress the liberationof histamine from mast cells in abdominal cavity of rat (Journal ofJapanese Society for Food Science and Technology, Vol.42, No. 11, p.952-958, 1955; and Allergy, Vol. 52, No. 1, pp. 58-64, 1997). However,there has been no report that polyphenols such as strictinin suppressthe production of IgE by B cells which is an origin of allergicreaction.

[0011] Pharmaceutical agents for allergic diseases have been developedand used for the therapy already but, since they have adverse actions,there has been a strong demand for antiallergic agents derived fromnatural products where a long-term administration is possible, safety ishigh and no adverse reaction takes place.

[0012] Thus, an object of the invention is to provide a therapeutic andpreventive agent for allergic diseases which has no adverse action,shows a high safety even by a long-term administration and is able to beutilized for food and/or beverage and cosmetic agent which are useddaily.

[0013] In order to solve the above-mentioned problems, the presentinventors have carried out a screening of substances having antiallergicaction using a suppressive action for the production of IgE as anindication and have found that polyphenols such as strictinin exhibitssuch an effect and, based upon such a finding, the invention has beenachieved.

SUMMARY OF THE INVENTION

[0014] The invention mentioned in claim 1 is an antiallergic agent whichis characterized in containing, as an effective ingredient, at least onepolyphenol selected from strictinin and methylated derivatives thereof.

[0015] The invention mentioned in claim 2 is an anti-inflammatory agentwhich is characterized in containing, as an effective ingredient, atleast one polyphenol selected from strictinin and methylated derivativesthereof.

[0016] The invention mentioned in claim 3 is the antiallergic agentaccording to claim 1 wherein the antiallergic agent is that for oraladministration.

[0017] The invention mentioned in claim 4 is the anti-inflammatory agentaccording to claim 2 wherein the anti-inflammatory agent is that fororal administration.

[0018] The invention mentioned in claim 5 is food and/or beveragecontaining an antiallergic agent for oral administration or ananti-inflammatory agent for oral administration which is characterizedin containing, as an effective ingredient, at least one polyphenolselected from strictinin and methylated derivatives thereof.

[0019] The invention mentioned in claim 6 is a method for the additionof an antiallergic agent for oral administration or an anti-inflammatoryagent for oral administration which is characterized in containing, asan effective ingredient, at least one polyphenol selected fromstrictinin and methylated derivatives thereof to food and/or beveragefor prevention, suppression and mitigation of allergic symptoms orinflammatory symptoms.

[0020] The invention mentioned in claim 7 is a cosmetic agent containingan antiallergic agent for external use or an anti-inflammatory agent forexternal use which is characterized in containing, as an effectiveingredient, at least one polyphenol selected from strictinin andmethylated derivatives thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021]FIG. 1 is a flow chart showing an example of a method for thepurification of strictinin;

[0022]FIG. 2 shows an influence of each of the fractionated fractions ona CεGT-inducible expression by IL-4;

[0023]FIG. 3 shows an influence of strictinin on a CεGT-inducibleexpression by IL-4 in human B cell line DND 39; and

[0024]FIG. 4 shows an influence of strictinin on a CεGT-inducibleexpression by IL-4 in human peripheral blood lymphocytes.

DETAILED DESCRIPTION OF THE INVENTION

[0025] Strictinin according to the invention is a compound representedby the following structural formula and, in addition to the saidcompound, a polyphenol which is a methylated derivative or a mixturethereof may be used in the present invention as well. Examples of thepolyphenol are those where galloyl group, digalloyl group, trigalloylgroup, hexahydroxyphenoyl group, 3-O-methylgalloyl group or4-O-methylgalloyl group is introduced into at least one of the hydroxylgroups at C1 to C4 and C6 of glucose.

[0026] Tea (Camellia sinensis) has been drunk from ancient time and hasbeen always taken for a long period and it has been noted that tea hasno bad affection to human body but is a beverage with a very highsafety. Accordingly, the tea leaf extract mainly comprising a polyphenolcompound such as strictinin used in the invention can be accepted asbeing taken without anxiety.

[0027] The polyphenols such as strictinin used in the invention can beseparated and collected from a polyphenol fraction obtained by anextraction of dried tea leaves such as “yabukita” tea leaves with anaqueous solvent. When the extract is utilized in and taken as foodand/or beverage, cosmetics, etc. in its final stage, it is preferredfrom the standpoint of safety that water, ethanol or a mixture thereofis used as a solvent.

[0028] Although there is no particular limitation for the ratio (byweight) of the tea leaves to the solvent, the ratio from 5 to 100 partsof the solvent to 1 part of tea leaves is preferred. With regard to thetemperature for the extraction, there is no particular limitation aswell and, usually, the range of from the room temperature to the boilingpoint of the solvent under an atmospheric pressure is preferred in viewof the operation. Time for the extraction is preferably with in a rangeof from 10 minutes to 6 hours.

[0029] The tea leaf extract mainly comprising polyphenols such asstrictinin used in the invention may be administered per se either as itis or after appropriately diluting with water or the like. It is alsopossible that it is made into a pharmaceutical preparation together witha commonly used pharmaceutical carrier. For example, the above-mentionedextract or the like can be made into a liquid preparation for oral usesuch as a syrup or made into a solid preparation for oral use such astablets, capsules, granules or diluted powder after processing intoextract, powder, etc. followed by compounding with a pharmaceuticallyacceptable carrier. With regard to the pharmaceutically acceptablecarrier, various organic or inorganic carrier substances which have beencommonly used as the materials for pharmaceutical preparations may beused and they are compounded as vehicles, lubricant, binder,disintegrator, etc. in a solid preparation or as solvent, excipient,suspender, binder, etc. in a liquid preparation. If necessary, additivesfor pharmaceutical preparations such as antiseptic, antioxidant,coloring agent, sweetener, etc. may be used as well.

[0030] Suitable examples of the vehicles or excipient are lactose, whitesugar (sucrose), D-mannitol, starch, crystalline cellulose and lightanhydrous silicic acid. Suitable examples of the lubricant are magnesiumstearate, calcium stearate, talc and colloidal silica. Suitable examplesof the binder are binding cellulose, white sugar, D-mannitol, dextrin,hydroxypropyl cellulose, hydroxypropyl methyl cellulose andpolyvinylpyrrolidone.

[0031] Suitable examples of the disintegrator are polyethylene glycol,propylene glycol, D-mannitol, benzylbenzoate, ethanol, trisaminomethane,cholesterol, triethanolamine, sodium carbonate and sodium citrate.Suitable examples of the solvent are purified water, ethyl alcohol andpropylene glycol. Suitable examples of the suspending agent aresurface-active agent such as ethanolamine stearate, sodiumlaurylsulfate, laurylaminopropionic acid, lecithin, benzalkoniumchloride, benzethonium chloride and glycerol monostearate andhydrophilic high-molecular compounds such as polyvinyl alcohol,polyvinylpyrrolidone, carboxymethyl cellulose, methyl cellulose,hydroxymethyl cellulose, hydroxyethyl cellulose and hydroxypropylcellulose.

[0032] Suitable examples of the antiseptic are p-hydroxybenzoates,chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid andsorbic acid. Suitable examples of the antioxidant are sulfites andascorbic acid.

[0033] The tea leaf extract mainly comprising polyphenols such asstrictinin used in the present invention may be administered either asit is or the extract is made into dry extract or powder to make in aform of food and/or beverage. It is compounded with a commonly usedmaterial for food and/or beverage and a carrier or the like which isacceptable for the manufacture of food and/or beverage and examples ofthe beverage are mixed tea drink, carbonate beverage, fruit beverage,lactic acid bacteria beverage, sport beverage and soybean milk. Examplesof confectionery are biscuit, chocolate, candy, chewing gum, snack cake,fried cake, western unbaked cake, Japanese cake, ice cream and jellycake. Examples of food are bread, noodle; processed soy bean productssuch as soybean curd; milk products such as yogurt and butter; meatproducts such as ham and sausage; omelet; fish meat paste products suchas kamaboko; condiments such as sauce, dressing, mayonnaise and fishflour; and meals such as curry, stew, hamburger and soup. They can beprepared by conventional methods.

[0034] Examples of the carrier which is acceptable in the manufacture offood and/or beverage are sweeteners such as sugar, glucose, fructose,isomerized liquid sugar, fructooligosaccharide, aspartame, sorbitol andstevia; coloring agents such as red cabbage dye, grape rind dye,elderberry dye, caramel, gardenia dye, corn dye, saffron dye andcarotene; preservatives such as decomposed pectin, benzoic acid, sorbicacid, p-hydroxybenzoates and potassium sorbate; pastes such as sodiumalginate, propylene glycol alginate, calcium cellulose glycolate andsodium cellulose glycolate; antioxidants such as L-ascorbic acid,tocopherol, erythorbic acid and rutin; coloring former such as ferroussulfate, sodium nitrite and potassium nitrite; bleaching agents such assodium hydrogen sulfite and potassium metabisulfite; quality maintainingagents such as propylene glycol; quality improving agents such asL-cysteine hydrochloride and calcium stearyllactate; inflating agentssuch as ammonium chloride, potassium hydrogen d-tartrate, ammoniumcarbonate, potassium carbonate, sodium hydrogen carbonate and alum;emulsifiers such as lecithin, sphingolipid, vegetable sterol, soybeansaponin, sodium alginate, propylene glycol alginate, sodium caseinate,glycerol fatty acid ester, sucrose fatty acid ester and sorbitan fattyacid ester; emulsion stabilizers such as sodium chondroitin sulfate;flavoring agents such as lemon oil, eucalyptus oil, peppermint oil,vanilla extract, orange oil, garlic oil, ethyl acetoacetate,anisaldehyde, ethylvanillin, cinnamic acid, citronellyl acetate, citral,vanillin, butyl butyrate and esters; enrichers such as L-ascorbic acid,L-asparagine, L-alanine, inositol, L-glutamine, carotene, tocopherol,vitamin A, folic acid, iron citrate, heme iron and non-calcined calcium;improving agents for wheat flour such as benzoyl peroxide, ammoniumpersulfate and chlorine dioxide; bactericides such as bleaching powder,hydrogen peroxide and hypochlorous acid; base materials for chewing gumsuch as methyl acetylricinolate, ester gum, vinyl acetate resin,polyisobutylene and polybutene; adherence preventers such as D-mannitol;binders such as sodium acidic pyrophosphate, potassium pyrophosphate andsodium pyrophosphate; acidic taste agents such as adipic acid, citricacid, gluconic acid, succinic acid, D-tartaric acid, lactic acid andDL-malic acid; seasonings such as fish/shellfish extract, yeast extract,sea tangle extract, soybean sauce, tomato puree, meat extract, mirin(Japanese sweet rice wine), fruit puree, dried bonito, sodiumL-aspartate, DL-alanine, L-arginine, L-glutamate, disodium 5′-inosinate,trisodium citrate, L-glutamic acid, sodium L-glutamate, succinic acid,L-tartaric acid and sodium lactate.

[0035] The tea leaf extract mainly comprising polyphenols such asstrictinin according to the invention is diluted with water or the like,concentrated or made into powder or granules followed by making intopharmaceutical preparation together with known pharmaceutical carriersto give the dosage forms such as aerosol, liquid, extract, suspension,emulsion, ointment, poultice, liniment or lotion. Or, if necessary,aqueous component, surface-active agent, oily component, solubilizer,moisturizer, powder component, alcohol, pH adjusting agent, antiseptic,antioxidant, thickener, dye, pigment, perfume, etc. which are known tobe used for cosmetics, semi-pharmaceuticals and pharmaceuticals areappropriately selected whereupon a desired form is prepared.

[0036] As an externally applied agent for the skin, it is possible tomake into the form of, for example, lotion, gel, emulsion, ointment,etc. whereby it is possible to provide as a cosmetic agent in variousforms including cosmetic lotions such as softening cosmetic agent andastringent cosmetic lotion; creams such as emollient cream, moisturecream and massage cream; milky lotions such as emollient milky lotion,nourishing milky lotion and cleansing milky lotion; make-up cosmeticssuch as face-washing agent, skin cleanser, foundation, eye color, cheekcolor and lipstick; hair cosmetics such as shampoo, rinse, hairtreatment, hair cream, hair dressing, hair tonic, pilatory and hairgrowing agent; bathing agents such as bath oil, bath salt and foam bath;etc.

[0037] In the present invention, polyphenols such as strictinin may beused in an appropriate amount taking the object for use, etc. intoconsideration and, for example, in the case of antiallergic agent oranti-inflammatory agent, the amount of 5-100 mg/kg or, preferably, 10-50mg/kg per day is appropriate.

[0038] When used in food and/or beverage, polyphenols such as strictininwhich are effective ingredients are used within a range of 5-100 mg/kgor, preferably, 10-50 mg/kg per day. Similarly, in the case ofcosmetics, polyphenols such as strictinin which are effectiveingredients are used within a range of 5-100 mg/kg or, preferably, 10-50mg/kg per day.

[0039] Incidentally, in any of the above cases, the amount may be usedonce daily or by dividing into several times a day.

[0040] Antiallergic agent and anti-inflammatory agent of the presentinvention and cosmetics containing the same are effective forprevention, suppression or mitigation of inflammation and the symptomscaused by allergic reaction. In addition, since such pharmaceuticalagents contain polyphenol compounds such as strictinin contained in teaas effective ingredients, safety is high and no toxic adverse action isnoted to human body even by administration for a long period wherebythey can be daily taken. Further, when food and/or beverage containing atea extract mainly comprising polyphenol compounds such as strictinin isdaily taken, it is useful for prevention and mitigation of the symptomsby allergic reaction.

EXAMPLES

[0041] In order to illustrate the invention in detail, representativeExamples and Experimental Examples will be given as hereunder althoughthe invention is not limited thereto.

Experimental Example 1 Extraction of Polyphenol Fraction from VariousTea Leaves (Tea Leaf Extract).

[0042] Tea leaves (100 g) dried with microwave were extracted with 50%methanol and the extracted fraction was extracted with 30% chloroform.Its aqueous phase was further extracted with ethyl acetate and the ethylacetate layer after the extraction was fractionated using an ODS column.An example of the method for the purification of strictinin is shown inFIG. 1. The fractionated fractions were named Fr. 1 to 5, respectively.All of Fr. 1 to 5 were once freeze-dried and then Fr. 1 to 2, Fr. 3 to 4and Fr. 5 were dissolved in water, 0.2% DMSO and 0.1% DMSO, respectivelyso that each fraction was made 1 mg/mL.

Experimental Example 2 Identification of Active Fractions.

[0043] Each of Fr. 1 to 5 in Experimental Example 1 was evaluated forits antiallergic action in vitro by a method for the expression of atranscript of an IgE heavy chain germline transcript which was toinvestigate the suppression of IgE production in human B cells (IgEclass switch suppression). This is a method utilizing the fact that,when human B cells are stimulated by IL-4 to induce the production ofIgE, a transcription is started from the upstream intron correspondingto an ε region (CE) in the constant domain gene of the Ig gene whereupona transcript (CεGT: germline transcript) is expressed and, after that, aclass switch of IgE is resulted by a DNA recombination. CεGT is an RNAwhich is always expressed before the IgE production is induced and theexpressed amount of CεGT is proportional to the class switch amount ofthe IgE gene. Therefore, when the degree of expressed amount of CεGT isdetected, it is possible to estimate the IgE class switch amount.

[0044] A method for the expression of an IgE heavy chain germlinetranscript was carried out according to the following procedures.

[0045] Human B cell line DND 39 (available from Hayashibara BiochemicalLaboratory) was prepared into 1×10⁵ cells/mL and stimulated by addingIL-4 thereto to make the final concentration 25U/mL. At that time, eachof Fr. 1 to 5 prepared in Experimental Example 1 in a concentration of10 μg/mL was added together with IL-4.

[0046] In the meanwhile, IL-4 (final concentration: 25 U/mL) and 2 ng/mLof a transforming growth factor β (TGF-beta; manufactured by Peprotech)were added to the above human cell line and the mixture was used as apositive control for suppressing the expression of CεGT.

[0047] They were incubated for 48 hours and centrifuged (300 ×g, 37° C.)to collect the cells and the total RNA was extracted with 1 mL of areagent for collection and extraction of RNA (trade name: Trizol;manufactured by Gibco BRL).

[0048] Then, a cDNA library was prepared according to the followingprocedure. First, concentration of the extracted total RNA was measuredby an absorptiometer, a portion of 10 μg was taken in a 0.6 mL tube andwater was added thereto to make 11.8 μL. To this were added each 1.0 Lof a 0.5 μg/μL oligo dT primer and a 20 μM CεGT antisense primer. Thetube was incubated at 70° C. for 10 minutes and quickly cooled in icefor 10 minutes and annealed to anneal mRNA, oligo dT primer and CεGTantisense primer. This was mixed with 2.0 μL of an RNase-free 10 mM dNTP(manufactured by Amersham), 4.0 μL of 5×buffer attached to anMMLV-reverse transcriptase (manufactured by Amersham), 0.1 μL of anRNase inhibitor (manufactured by Takara Shuzo) and 0.1 μL (finalconcentration: 20-200 units/tube) of an MMLV-reverse transcriptase. Themixture was incubated at 37° C. for 1 hour to synthesize cDNA. Thesynthesized cDNA was amplified by a PCR. Sense and antisense primerswere prepared based upon a base sequence of human GAPDH and CεGTregistered at the Gene Bank. The structures are shown in the SequenceListing. Thus, a CεGT sense primer, a CεGT antisense primer, a humanGAPDH sense primer and a human GAPDH antisense primer are shown in SEQID NO:1, NO:2, NO:3 and NO:4, respectively.

[0049] CεGT-DNA was amplified using the said primer by a polymerasechain reaction (PCR) method. As a template for the PCR, 1 μL of anoriginal solution of cDNA was used and, for the detection of CεGT, 0.8μL of 10 mM dNTP, 0.5 μL of sense primer, 0.5 μL of antisense primer,0.1 μL of AmpliTaq Gold (manufactured by Perkin Elmer) and 1 μL of10×buffer attached to the AmpliTaq Gold were mixed and distilled waterwas added thereto to make the total volume 10 μL.

[0050] For the detection of GAPDH, 0.8 μL of 10 mM dNTP, 1 μL of MgCl₂,0.5 μL of sense primer, 0.5 μL of antisense primer, 0.1 μL of Taqpolymerase (manufactured by Fermentas) and 1 μL of 10×Taq bufferattached to the Taq polymerase were mixed and distilled water was addedthereto to make the total volume 10 μL.

[0051] A PCR was carried out using a GeneAmp PCR System 2400(manufactured by Perkin Elmer) and the condition therefor was asfollows. Thus, for the detection of CεGT, a cycle of 95° C. for 30seconds, 60° C. for 30 seconds and 72° C. for 30 seconds was conductedfor 15 cycles and, finally, a reaction was carried out at 72° C. for 7minutes. For the detection of GAPDH, a cycle of 95° C. for 30 seconds,60° C. for 30 seconds and 72° C. for 30 seconds was conducted for 10cycles and, finally, a reaction was carried out at 72° C. for 7 minutes.After that, the resulting PCR product was subjected to anelectrophoresis using an agarose gel for separation (concentration: 1%;manufactured by Sawadi Technology). After completion of theelectrophoresis, it was transcribed to a plus-charged Nylon membrane(manufactured by Amersham) (a southern transfer).

[0052] After that, a hybridization was carried out on the Nylon membraneto which the migrated pattern was transcribed using an oligo DNAfluorolabeled with CεGT-DNA which was amplified for 15 times in theabove-mentioned PCR [which was prepared in such a manner that anoligonucleotide (SEQ ID NO:5 of the Sequence Listing) was picked outfrom a region pinched by the above-mentioned sense and antisense primersused for the PCR based on a base sequence of human CεGT and then theoligonucleotide is applied to an oligo labeling kit (manufactured byAmersham)] as a probe. After the hybridization, a reaction with CDP-Star(Amersham) which was a fluorescence detecting agent was carried out andthe expressed amount of CεGT was measured from the resultingfluorescence intensity. FIG. 2 shows an influence of each fraction onCεGT inducible expression by IL-4 in the human B cell line DND 39. Inthe drawing, GAPDH means glyceraldehyde-3-phosphodehydrogenase and □shows a control.

[0053] As will be apparent from FIG. 2, the expressed amount of CεGT wassuppressed in the fraction of Fr. 3 as compared with other fractions.From that fact, it was found that an active component was available inthe fraction of Fr. 3 and, after that, the fraction was finelyfractionated using an ODS column whereupon one of the fractions wasfound to be a fraction containing strictinin only.

Experimental Example 3 Measurement of Antiallergic Activity in Human BCell Line.

[0054] Strictinin which was identified as an active component inExperimental Example 2 was used for measuring the antiallergic activityin human B cell line according to the same way as in the method for theexpression of an IgE heavy chain germline transcript mentioned inExperimental Example 2. Incidentally, strictinin was added at the sametime with IL-4. The adding concentrations of strictinin were 1, 10 and25 μM. FIG. 3 shows an influence of strictinin on the CεGT inducibleexpression by IL-4 in the human cell line DND 39. In the drawing, GAPDHshows glyceraldehyde-3-phosphodehydrogenase and □ shows a control.

[0055] As shown in FIG. 3, it was apparent that, in the human B cellline, strictinin strongly suppressed the IgE class switch by addition ofIL-4. Since IgE is an immunoglobulin deeply participating in theallergic reaction, the fact that IgE class switch is suppressed meansthat antiallergic activity is available.

Experimental Example 4 Measurement of Antiallergic Activity in HumanPeripheral Blood Lymphocytes.

[0056] Human peripheral blood normal cells (monocytes; separated fromthe blood which was collected from a healthy human volunteer) was usedinstead of the human B cell line DND 39 of Experimental Example 3 and anantiallergic activity was measured by the same way as in the method forthe expression of an IgE heavy chain germline transcript mentioned inExperimental Example 2. Like in Experimental Example 2, strictinin wasadded at the same time with IL-4. Incidentally, the adding concentrationof strictinin was made 25 μM. FIG. 4 shows an influence of strictinin onthe CεGT inducible expression by IL-4 in the human peripheral bloodlymphocytes. In the drawing, GAPDH showsglyceraldehyde-3-phosphodehydrogenase and □ shows a control.

[0057] As shown in FIG. 4, strictinin strongly suppressed the IgE classswitch by addition of IL-4 in the human peripheral blood lymphocytes andwas noted to have an antiallergic activity.

Example 1 Manufacture of Candy

[0058] Candy was manufactured by a conventional method using thefollowing materials. As to a polyphenol fraction containing strictinin,etc., Fr. 3 in Experimental Example 1 was used (the same one was used inall the following Examples as well). Powdery sorbitol 97.7 g Perfume 0.2 g Sorbitol seed 0.05 g Polyphenol fraction containing strictinin,etc. 0.05 g Total  100 g

Example 2 Manufacture of Chewing Gum.

[0059] Chewing gum was manufactured by a conventional method using thefollowing materials. Gum base   20 g Calcium carbonate    2 g Stevioside 0.1 g Polyphenol fraction containing strictinin, etc.  0.05 g Lactose76.85 g Perfume    1 g Total   100 g

Example 3 Manufacture of Bathing Agent.

[0060] A bathing agent containing a tea leaf extract mainly comprisingstrictinin was manufactured by a conventional method using the followingmaterials. Dry sodium sulfate  53 g Sodium hydrogen carbonate  40 gLight calcium carbonate  1 g Silicic acid anhydride  1 g Polyphenolfraction containing strictinin  5 g Perfume a little Pigment a littleTotal 100 g

[0061] Sequence Listing

[0062] <110>Hiroshi Nakamura, Director-General of National Institute ofVegetables, Ornamental Plants and Tea, Ministry of

1 5 1 25 DNA ARTIFICIAL SEQUENCE ARTIFICIAL DNA 1 aggctccact gcccggcacagaaat 25 2 25 DNA ARTIFICIAL SEQUENCE ARTIFICIAL DNA 2 acggaggtggcattggaggg aatgt 25 3 22 DNA ARTIFICIAL SEQUENCE ARTIFICIAL DNA 3gctcagacac catggggaag gt 22 4 22 DNA ARTIFICIAL SEQUENCE ARTIFICIAL DNA4 gtggtgcagg aggcattgct ga 22 5 25 DNA ARTIFICIAL SEQUENCE ARTIFICIALDNA 5 agctgtccag gaacccgaca gggag 25

What is claimed is:
 1. An antiallergic agent which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient.
 2. An anti-inflammatory agent which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient.
 3. The antiallergic agent according to claim 1, wherein the antiallergic agent is that for oral administration.
 4. The anti-inflammatory agent according to claim 2, wherein the anti-inflammatory agent is that for oral administration.
 5. Food and/or beverage containing an antiallergic agent for oral administration or an anti-inflammatory agent for oral administration which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient.
 6. A method for the addition of an antiallergic agent for oral administration or an anti-inflammatory agent for oral administration which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient to food and/or beverage for prevention, suppression and mitigation of allergic symptoms or inflammatory symptoms.
 7. A cosmetic agent containing an antiallergic agent for external use or an anti-inflammatory agent for external use which is characterized in containing at least one polyphenol selected from strictinin and methylated derivatives thereof as an effective ingredient. 